The Malaria Family Tree Leads Back to Birds

Holly Lutz is out for blood. Crawling through a cramped cave to find bats, she can feel the tickle of antennae from cave crickets coating the walls, inches away. The smell of guano guides her to the cavernous roost site, where sleepy bats hang like fruit from the walls. This young Cornell Lab of Ornithology researcher has spent years collecting blood samples from birds, bats, and small mammals across five East African countries. Her goal is to clarify the evolution of a single-celled organism that originated at least half a billion years ago.

Malaria. Despite all our medical advances, the Centers for Disease Control (originally created to fight malaria in the United States) reports that about half-a-million people die of the disease each year and many more are sickened, mostly in poor, undeveloped countries. Malaria was eradicated in the U.S. in the 1950s. The cases reported now are found in people who travel here from the more than 100 countries where malaria is still a big problem. Children and pregnant women are especially vulnerable.

In a paper published in the journal Molecular Phylogenetics and Evolution, Lutz and co-authors present their analyses of DNA for 170 lineages of malaria parasites found in collected blood samples, shedding light on the little-known malarial family tree. She says the evidence strongly supports their hypothesis about the origin of malarial parasites and which mammal was infected first.

“Malaria parasites first infected reptiles and birds millions of years ago,” Lutz explains. “Our analyses show that over a long period of time and many genetic mutations later, a parasite jumped from birds into the small Miniopterus bat, which as far as we now know was the first mammal to be infected by malaria. Once established in this group of bats, the parasite was able to switch hosts again, infecting other bats and mammals, including rodents and primates.”

Birds were once thought to be the original hosts of the malaria species that now infects humans. To test that hypothesis, Lutz wanted to analyze blood parasites from many more mammals and birds to see which malarial lineages were most closely related to the deadly Plasmodium falciparum in humans.

“The kind of information we present along with other ongoing research will eventually allow us to answer the question ‘when did humans first become infected with malaria?’” Lutz explains. “Then we can begin to figure out if the jump to humans matches up with other key historical events–perhaps a geological event, movement of humans from one area to another, or the introduction of rodents into a new part of the world.”

All of this work has grown out of Lutz’s long-time collaboration with The Field Museum of Natural History in Chicago, where scientists have an ongoing project studying vertebrate biodiversity in East Africa. Lutz has participated in a number of their African expeditions, including a 2009 pilot project to sample parasites and pathogens among birds and small mammals in Malawi. Lutz was stunned when she examined these blood samples.

“I found mind-blowing diversity among malarial parasites in the African birds,” Lutz says. In a research paper published last year, Lutz and colleagues reported the discovery of nearly 250 unique genetic lineages of malarial parasites in birds, 201 of which were new to science. Lutz points out that this amazing diversity suggests some form of malaria can be found nearly everywhere, though not necessarily the kind adapted to survive in humans.

In fact, there’s no danger of getting human malaria from a bird or a bat. Lutz says humans, birds, bats, and other animals can only be infected by a malaria species evolved to survive in a specific host. Host switching is rare and takes thousands or millions of years to accomplish.

Vital links in the transmission of malaria are blood-feeding insects in the group known as “dipterans.” Just as there are hundreds of species of malarial parasites, there are many species of insects that can transmit malaria, most of which feed exclusively on one creature or another. Humans are infected by mosquitoes, while wingless bat flies transmit some forms of bat malaria. The vast majority of these “insect vectors” are poorly known, including whatever insect transmitted malaria from birds to bats in the distant past. To call this work “complex” is a vast understatement. Lutz is undaunted.

“We want to continue sampling—we still have a lot of basic biodiversity exploration to do in Africa and other areas of the world,” she says. “The work in remote wild places can sometimes be dangerous or intimidating, but mostly it’s exhilarating.”

After defending her dissertation in May, and before starting an NSF postdoctoral appointment at the Field Museum, Lutz plans to return to Africa on a blood and tissue sampling expedition to Zika Forest of Uganda. This is where the headline-grabbing Zika virus was first discovered by the Uganda Virus Research Institute. She hopes to contribute to the CDC’s effort to identify the natural reservoir of the virus, which may be linked to birth defects in newborns.

“The more we know, the more empowered we are to protect life,” Lutz says. “For me it’s always been about the thrill of discovering new species. There is so much out there to be discovered. And parasites are the coolest!”

Holly Lutz is currently finishing her Ph.D. in the Cornell Departments of Ecology and Evolutionary Biology and Population Medicine and Diagnostic Sciences. This summer she plans to continue her research with trips to Uganda and Kenya. After completing her Ph.D. in May 2016, she will be joining the lab of Dr. Jack Gilbert at the University of Chicago as an NSF Postdoctoral Fellow, while continuing to work closely with The Field Museum and African colleagues.

Reference

Holly L. Lutz, Bruce D. Patterson, Julian C. Kerbis Peterhans, William T. Stanley, Paul W. Webala, Thomas P. Gnoske, Shannon J. Hackett, and Michael Stanhope. Diverse Sampling of East African Haemosporidians Reveals Chiropteran Origin of Malarial Parasites in Primates and Rodents, Molecular Phylogenics and Evolution. March 2016.